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Cancer Cells and Metastasis · Journal article
Acs Sensors · August 11, 2026
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This study presents the first application of electrical impedance spectroscopy (EIS) to measure viability of individual 3D liver cancer spheroids in a label-free, noninvasive manner. EIS responses at optimized frequency pairs correlated with viability changes induced by dimethyl sulfoxide and doxorubicin, and results were consistent with conventional fluorescence and ATP assays. The work establishes technical feasibility and transferability across treatments but remains a methodological proof-of-concept without demonstration of clinical utility or superiority in drug screening workflows.
Proof-of-concept methods validation study with in vitro controls. Liver cancer spheroids cultured in vitro and treated with dimethyl sulfoxide or doxorubicin at varying concentrations.. Intervention: Electrical impedance spectroscopy (EIS) using six probing frequencies with an optimized frequency pair for viability assessment. Compared with: Conventional viability assays: fluorescence imaging and ATP quantification.
EIS successfully enabled label-free viability profiling of individual spheroids independent of spheroid size Optimized frequency pair detected viability changes for both dimethyl sulfoxide and doxorubicin treatments EIS method reflected viability changes and revealed inter- and intra-treatment group differences with single-spheroid resolution compared to conventional assays
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This methodological advance offers a potential tool for accelerating drug screening in 3D models; however, clinical relevance remains to be established through integration into actual discovery pipelines and comparison of predictive accuracy against clinical outcomes.
First-in-application proof-of-concept study demonstrating label-free viability profiling of individual spheroids using EIS; validation against conventional assays is present but the work is methodological, single-center, and lacks clinical outcome or disease-relevant efficacy data.
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This methodological advance offers a potential tool for accelerating drug screening in 3D models; however, clinical relevance remains to be established through integration into actual discovery pipelines and comparison of predictive accuracy against clinical outcomes.
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Three-dimensional (3D) cell models, such as spheroids and organoids, are powerful tools to enhance the predictive power of preclinical in vitro studies and support clinical translation of anti-cancer therapies. However, their integration into drug discovery pipelines remains limited, particularly for high-throughput screening, where rapid and reliable viability assessment is essential. Conventional viability assays, often dye-based or destructive, remain labor-intensive and poorly suited for high-throughput applications and downstream re-use of the models. In this study, we demonstrate, for the first time, that electrical impedance spectroscopy (EIS) enables label-free viability profiling of individual spheroids. For this purpose, a differential EIS sensor was integrated into a plastic microfluidic chip in flow-through configuration with self-aligned facing electrodes. Using six probing frequencies, we measured the EIS responses of liver cancer spheroids exposed to varying concentrations of dimethyl sulfoxide and doxorubicin, a chemotherapeutic compound. We identified an optimized frequency pair that enabled us to monitor spheroid viability, independent of spheroid size. Comparison with conventional viability assays, namely fluorescence imaging and ATP quantification, confirmed that the EIS method reliably reflected viability changes and revealed inter- and intra-treatment group differences owing to the method's single-spheroid resolution. The same frequency pair could be used to detect viability changes for both compounds, suggesting transferability of the EIS method across treatments. Furthermore, we showed that utilizing additional EIS features improved classification of spheroids with subtle viability differences. Together, these results demonstrate that EIS is a promising approach for noninvasive, single-spheroid viability profiling and a valuable tool for high-throughput drug screening with spheroid models.
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